Nucleic acid-based therapeutics are quickly emerging and have been considered as an alternative or adjuvant to the chemical antiviral agents currently used to treat HIV-1/AIDS. The combinatorial use of various antiviral nucleic acids could be more efficacious in blocking viral replication and preventing the emergence of resistant HIV-1 variants (1,2). Additionally, owing to their favorable characteristics, such as small size, high stability (dehydrated form), lack of immunogenicity, facile chemical synthesis, adaptable modification and cell-free evolution, highly specific nucleic acid-based aptamers and aptamer-functionalized agents have been used extensively for targeted disease therapy (3-7}.
To date, many nucleic acid aptamers specific to various parts of the HIV-1 genome and HIV-1 dependent proteins, including HIV-1 reverse transcriptase (RT), integrase (IN), nucleocapsid (NC), Gag, TAR, Rev, Tat, envelope gp120 and CD4 protein, have been raised through the purified protein-based SELEX method and shown to effectively suppress viral replication (3,8,9) Importantly, a number of cell-specific aptamers targeting cell surface proteins have been adapted as promising delivery vehicles for the targeted delivery of small interfering RNA (siRNA) in a cell-type-specific manner (10,11). The potential combined use of siRNAs and aptamers is intriguing as it could effectively block viral replication and prevent the emergence of resistant variants (12).
In previous studies, anti-HIV gp120 aptamers were combined with anti-HIV siRNAs to achieve a dual-inhibitory drug capable of delivering siRNAs selectively to HIV-infected cells as well as inhibiting viral entry via blocking of the envelope interaction with the CD4 (13-15).